Common local drug-related adverse events occurring in at least 10% of patients in Study 301 were hematuria, dysuria, urinary tract infection, pollakiuria, and micturition urgency. Fatigue was the most common systemic adverse event.
Two drug-related serious adverse events occurred: moderate hematuria and severe urinary tract infection, Dr. Cohen said. Four deaths occurred during the study, but none were thought to be drug related.
The study did not enroll BCG-naive patients, so it is unclear whether MCNA may be altered by BCG or whether prior BCG is necessary to prime responses to MCNA. In vitro data using a prior formulation of the drug suggested benefit in BCG-naive patients, but it was noted that MCNA is eliminated more quickly than BCG and that de novo studies would be needed to sort out this issue.
One panelist pointed out the practical consideration that BCG shortages have been a frequent problem for patients, despite the drug’s being around for decades, and that there may be some pressure to use MCNA first-line if BCG is unavailable. Cost data were not provided for BCG.
Dr. Patrick C. Walsh, professor and director of Brady Urological Institute at Johns Hopkins Medical Institutions, Baltimore, agreed that the action of MCNA may be limited, but voted in favor of approval.
“My concern was delay in cystectomy and I’ve been convinced at this meeting that if you delayed cystectomy for 6 months and you gave this drug and it didn’t work, I don’t think the patient would be harmed,” he said.
CTGTAC chair Dr. Timothy P. Cripe of Ohio State University, Columbus, also voted in favor, noting that the risk:benefit ratio was favorable because there is clearly some benefit to the drug and very little risk.
“With immunotherapies on the rise, if this were approved, I’m sure there’d be a lot more trials and combinations that would augment its activity,” he added.
CTGTAC member Dr. Bruce J. Roth of Washington University, St. Louis, voted no because of the quality of the data, but suggested, as did others, that he would like MCNA to return before the FDA in other, better-designed trials.
The initial vote was 19 for and 6 against approval, but it was discovered that one vote was made via proxy, which is not allowed, and the official record was amended to 18 for and 6 against.
MCNA was granted priority review status in September and the Prescription Drug User Fee Act (PDUFA) date set was for Feb. 27, 2016. Following news of the negative vote, Telesta’s share price fell 50%.
Members of FDA advisory panels have been cleared of potential conflicts of interest by the FDA prior to the meeting.